Metformin: A Journey from countryside to the bedside

The discovery of metformin as an anti-diabetic drug spans three centuries-beginning in the herb, Galega officinalis in the 17 th century and ending in its launch as Glucophage in the 20 th century. Extract from the leaves of G. officinalis was used to treat many ailments such as fever, plague and symptoms of diabetes. The herbal extract contains guanidine and galegine as major chemical components. These compounds, although had an anti-diabetic effect, were too toxic for clinical use. Discovery of antimalarial drug, paludrine which also had blood glucose lowering activity, at the Imperial Chemical Industries, UK prompted evaluation of paludrine analogues, as potential anti-diabetic agents. This speculation was also based on the structure of paludrine, which partly resembled galegine, a compound present in the extract of G. officinalis. This development coupled with Garcia's positive results using flumamine, a guanidine analogue, on 'flu' fever accelerated the evaluation of guanidine and galegine analogues for anti-diabetic activity. These efforts culminated in the discovery of metformin, introduced as 'Glucophage', by Jean Sterne, in 1957. In this article, we have highlighted the journey of metformin from a common countryside herb to its present day status of a 'Wonder Drug' sitting at the bedside of diabetic patients.